Background: Low density lipoprotein receptor-related protein-1 (LRP-1) is highly expressed in the central nervous system and plays a role in neurodegenerative disorders. The available data on this subject-matter seem to support the presence of a correlation between LRP-1 levels and abnormal aggregation of a plurality of proteins, including tau, amyloid, and α‑synuclein. Understanding the molecular mechanisms underlying Parkinson’s disease (PD) is critical for development of new therapies. Aim: To investigate serum soluble LRP-1 (sLRP-1) concentrations in patients with PD and explored their potential role as a biomarker in diagnosis and prognosis of disease. Methods: Based on well-defined inclusion and exclusion criteria, we have included 133 PD patients and 45 healthy controls. The clinical severity was assessed using Hoehn Yahr and Unified PD Rating Scale (UPDRS). Following a fasting period, venous blood samples were taken, and centrifuged. Serum samples were stored until analysis. sLRP-1 was measured by ELISA assay. Results: The median of serum sLRP-1 levels was higher in PD patients compared to that in healthy controls, but without reaching a statistical significance. There was a positive, but statistically insignificant, correlation between sLRP-1 levels and duration of disease. sLRP-1 levels had a significant correlation with UPDRS Parts I and IV. Patients with hypertension showed lower levels of sLRP-1. Conclusion: The present study suggests that serum sLRP-1 concentrations are associated with the factors influencing prognosis of PD and disease severity. Further studies are needed to definitively determine whether or not sLRP-1 can be utilized as a diagnostic and prognostic biomarker for PD.